Accelerated nephrotoxic nephritis is exacerbated in C1q-deficient mice

C1q deficiency strongly predisposes to the development of systemic lupus er ythematosus in humans and mice. We used the model of accelerated nephrotoxi c nephritis in C1q-deficient mice to explore the mechanisms behind these as sociations. C1q-deficient mice developed severe glomerular thrombosis withi n 4 days of induction of disease, whereas wild-type mice developed mild inj ury. These findings suggest that C1q protects from immune-mediated glomerul ar injury. This exacerbated thrombosis was also seen in mice triply deficie nt in C1q, factor B, and C2, excluding a major pathogenic role for the alte rnative pathway of complement in this phenomenon. However, these mice did n ot develop elevated creatinine levels. No exacerbation of accelerated nephr otoxic nephritis was observed in mice doubly deficient in factor B and C2, suggesting a protective role for C1q against renal inflammation that is pro ximal to C2 activation. There were increased murine IgG deposits, neutrophi l numbers, and apoptotic cells in the glomeruli of C1q-deficient mice compa red with wild-type mice. Renal expression of genes encoding procoagulant pr oteins was also enhanced in C1q-deficient mice. The increased IgG deposits and apoptotic cells in the glomeruli of C1q-deficient mice suggest that the exacerbation of disease may be due to a defect in the clearance of immune complexes and/or apoptotic cells from their kidneys.